PROJECT SUMMARY Chlamydia trachomatis, the most common sexually transmitted bacterial pathogen, annually infects approximately 100 million men and women worldwide. Depending on the population studied, about 5-20% women are positive for Chlamydia during their reproductive age. Since 50% of infections are asymptomatic, it is very difficult to identify and treat this group of people. If a Chlamydia infection is not diagnosed or treated properly during pregnancy, 70% of babies born from infected mothers acquire the infection from their mothers. Many preclinical animal models of genital infections were established using set numbers of Chlamydia as inoculation doses. However, very few studies were performed in which animals were infected by sexual intercourse. Recently, we have developed a mouse model of sexual transmission of Chlamydia in which C. muridarum was transmitted sexually from infected male mice to female mice and from sexually infected female mice to newborn mice. The goal of this proposal is to develop a transmission-blocking vaccine that will prevent Chlamydia transmission not only from male mice to female mice but also from sexually infected female mice to newborn pups. As a vaccine candidate we will use Chlamydia outer membrane protein complex (COMC) since it has been shown earlier that COMC was able to elicit protection in mice against a genital infection and infertility. In addition, COMC has several immunodominant membrane proteins including the major outer membrane protein, the 60 kDa cysteine rich protein, the 12-15 kDa cysteine rich proteins, and the putative outer membrane proteins, in their native conformational forms. COMC can be produced in large scale with a little laboratory manipulations. So far no studies have been performed to examine COMC's ability to prevent sexual transmission in female and newborn mice. The hypothesis of the study is that COMC-specific Th1 plus Th2-specific immunity in female mice will block sexual transmission of Chlamydia from infected male mice to female mice and from female mice to pups. Two specific aims will be studied. Specific Aim 1 will identify potential human adjuvant(s) and the route of COMC delivery for eliciting a transmission-blocking immunity in female mice against chlamydial transmission. Specific Aim 2 will identify the boosting strategies of COMC on nursing dams so that dams can supply protective immune components, especially antibodies and Th1 cytokines, to pups through milk. This will be the first vaccine study focusing on the prevention of sexual transmission of Chlamydia in two hosts. This sexual transmission model parallels human infections and this study will adopt an immuno-molecular approach to identify human adjuvants. The results of this study will help us to design a transmission-blocking vaccine for humans against genital chlamydial infections.